Oxidative coupling is a common and efficient method used to convert thiol compounds into organic disulfide compounds. The reaction commonly involves coupling of two thiol molecules, and often employs oxidants such as hydrogen peroxide and molecular oxygen in conjunction with one or more catalysts to promote the coupling reaction. Aerobic oxidation is one of the most common methods used due to wide-availability of oxygen and the generation of water as the only theoretical reaction byproduct. A number of oxidation systems have been reported, but many are known to induce overoxidation to generate side products including thiosulfinates, thiosulfonates, and sulfonic acids. These overoxidation products not only reduce the quantity of disulfide obtained from the coupling reaction, but often necessitate additional synthetic operations including complicated workups and purifications. While thiols naturally undergo oxidative coupling in the presence of oxygen, a transition metal catalyst is often employed to obtain disulfides with lower temperatures and shorter reaction times. Many existing methods require the use of appreciable amounts of transition metal compound because the catalysts are often ineffective at promoting oxidative coupling at low catalyst loading. Thus, existing methods can be quite expensive due to the cost of the metal catalyst employed. Moreover, additional purification steps may be needed to remove the large quantities of metal impurities present in the disulfide product.
There is an ongoing need for efficient, cost-effective methods of producing organic disulfide compounds in high yield. The method should generate disulfides having low impurity content, and require little to no purification of the disulfide product.